Clostridium difficile is the most common identified cause of antibiotic associated diarrhea, accounting for 15%-25% of cases (Bartlett, 1994, Clin. Infect. Dis., 18 (Suppl 4): S265-272). C. difficile infection (CDI) encompasses a wide range of clinical syndromes from simple diarrhea to pseudomembranous colitis associated with significant morbidity and mortality. There has been a marked increase in the incidence and severity of CDI in recent years, and in 2001, there was a 42% increase in U.S. short-stay hospital discharge diagnoses of CDI. There was a further increase of 25% between 2003 and 2004 and another 10% in 2005. The increase was greatest in patients >64 years of age and occurred in most geographic areas of the country. C. difficile-related mortality rates per million of United States population rose from 5.7 in 1999 to 23.7 in 2004, and there were an estimated 26,642 deaths due to CDI during 1999-2004.
In 2000, a more severe form of CDI was identified in the U.S. and Canada and also in Europe. Many cases of this severe form of CDI have been shown to be caused by an “epidemic” strain of C. difficile, which has been characterized as “BI” by restriction enzyme analysis (REA), “NAP1” (North American Pulsed Field Type 1) by pulsed field gel electrophoresis, and “027” by PCR ribotyping. In addition, it has been characterized as “toxinotype III” (by REA of toxin genes). In prior years, the great majority of “non-epidemic” hospital strains of C. difficile belonged to toxinotype 0. This BI/NAP1/027 “epidemic” strain has been shown to be a hyperproducer of toxins A and B, which may be the primary reason for the increased virulence of the epidemic strain. The tcdC gene, within the pathogenicity locus of the “epidemic” strain, appears to be a negative regulator of toxin A and B production. 